29: Principles of Local Anesthetic Flashcards
What do all local Anesthetics have In common? (What is their very gross MOA?)
Drugs which reversibly block neuronal conduction when applied locally
Recap: How is a neural AP generised?
- Na+ channels open–> Na+ influx leads to depolerisation
- Na+ channels close, K+ channels open leading to K+ efflux and repolierisation
- too far: hyperpolerisation
- Restored to normal
Summarise the common structural characteristics of local anesthetics
All have 3 things in common
- aromatic region (for benzine-like properties)
- central ester/amide bond
- defines the two classes of LA
- Basic amine side-chain
What are the two Classes of Local Anesthetics?
Name an example for each
Determined by the bond that links the aromatic ring and amine side chain
- Esters (e.g. Cocaine)
- Amides (e.g. Lidocaine)
What are hte different MOA of local Anesthetics
- Mainly: Hydrophilic pathway
- But also: Hydrophobic pathway
- might also influenct channel gating
- prolong inactive state of sodium channels
Explain the Hydrophilic pathway in the MOA of local Anesthetics
- Unionised form of LA diffuses across
- connective tissue membrane
- axonal membrane
- Gets ionised intracellulary
- Ionised form goes into open Na+ channel and blocks it from the inside
- No Exitation of Neuron
Explain the use-dependancy of LAs
Use dependant because
- Hydrophilic pathway works by entering channels in open form
- is nocioceptors are more active–> more open channels
Explain the Hydrophobic MOA of LA
Minor role (mainly Hydrophilic)
- lipid soluble LA diffuse in membrane and directly block NA+ channels from membrane
What are the cellular effecs of an LA?
- prevents generation and conduction of AP
- No direct influence on resting membrane potential
- might influence channel gating
- leave Na+ channels inactivated for longer
Explain the selectivity of LA
It has the main effects on
- small diameter fibres (e.g. A delta and C-firbes)
- non-myleinated fibres (easier to access)
- generally: good effect on sensory fibres and only limited effect on motor nerves
Name the different ROA for LA
- Topical (Surface Anaesthesia)
- Infiltration Anaesthesia
- IV regional Anaesthesia
- Nerve block Anaesthesia
- Spinal Anaesthesia
- Epidural Anaesthsia
What are the sites, formulation and concentration of Surface anaesthesia in the use of LA
- Expecially on Mucosal Surfaces (e.g. mouth, bronchial tree)
- Spray or powder
- high concentration needed –> risk of systemic toxicity
What is the mechanism and indication of Infiltration anaesthesia in the administration of LAs
- Directly into tissues → sensory nerve terminals
- often Adrenaline co-injection
- causes vasoconstriction which limits dosage, risk of systemic toxicity and bleeding
- (NOT extremities (e.g. digits) to avoid ischaemia
- often Adrenaline co-injection
- Used in Minor surgery
How would you administer LA in Intravenous regional anaesthesia?
What are the implications and risks?
- i.v. administration distal to pressure cuff
- E.g. in Limb surgery
- Systemic toxicity in premature cuff release
Explain the Mechanism and use of Nerve block anaesthesia in the application of LAs
- Close to nerve trunks e.g. dental nerves
- Widely used – low doses required
- but: slow onset
- Vasoconstrictor co-injection
Explain the
- site of injection
- use and
- side effects of
A spinal anaesthesia use in administration of LA
- Site of injection: subarachnoid space –> around spinal routes
- Low dose
- uesd in surgeries of Abdomen, pelvis,
Explain the side effects of a spinal anaesthesia use in administration of LA
- ↓ b.p. –> due to block of preganglionic SNS fibres
- prolonged headache
- due to LA goint via CSF into brain
Why might Glucose be added to a LA in a spinal anaesthesia?
To increase its specific gravity
- gives better control over effect due to its distribution via tilting table
Where is an Epidural anaesthesia administered?
What are its advantages and disadvantages compared toa spinal anaestesia?
Administerd in fatty tissue in epidural space
- has same indication + childbirth but also
- slower onset of action
- higher doses that are required (increased risk of systemic toxicity)
- Advantages
- more resticted action
- less effect on BP decrease
What are the Pharmacokinetic properties of most LAs?
E.g. Lidocaine (Amide)
- good absorbtion in mucus membrane
- weak base
- 70% Plasma protein bound
- t 1/2 and Duration of action 2h
What is the Metabolism of Lidocaine?
Hepatic
N-dealkylation (split of of alkyl group)
Why is more LA required in infected tissue?
Becaue infected tissue is acidic
- LA are weak bases
- more ionised and less able to get into nerves
- higher dose needed
What are the Pharmacokinetic properties of Cocaine when used as an LA?
- good absorbtion over mucus membranes
- 90% plasma protein bound
- t 1/2 about 1h
*
Explain the metabolism of Cocaine
Metabolised in Liver and plasma by
Non-specific esterases
What are the Side effects of most LA on the CNS ?
Paradox effects at low doses (at high doses depressant but)
- stimulation
- restlessness, confusion
- tremor
–> possibly due to inhibition of GABA neurons
What are the side effects of Lidocaine (and most LA) on the CVS?
- myocardial depression
- vasodilatation
- ↓ b.p.
Due to Na+ block —> less exitation
What are the Side effects of Cocaine used as an LA?
Overall: caused not by NA+ block but by SNS stimmulation (inhibited reuptake)
- CNS
- euphoria, exitation
- CVS
- increased CO
- vasoconstriction
- increase in BP
Which LA is often used in epdiural of spinal anaesthesia?
Why?
Bupivacaine
due to longer duration of action (doa about 6hr)
